Chronic kidney disease (CKD) is a known predictor of cardiovascular morbidity and mortality, and is an important risk factor for atrial fibrillation (AF). Very little remains known about the molecular mechanisms underlying AF associated with CKD. Our preliminary data reveal activation of the NLRP3 inflammasome within atrial myocytes isolated in a mouse model of CKD. The long-term goal of this project is to elucidate the molecular and cellular mechanisms underlying AF development as a result of inflammasome activation in mice with CKD. We will test the hypothesis that enhanced activation of the NLRP3 inflammasome within atrial myocytes enhances the susceptibility to AF by promoting proarrhythmogenic Ca2+ releases via increased SPEG-phosphorylation of RyR2.